Prevalence and Burden of Illness of Migraine in Managed Care Patients

OBJECTIVES: To determine the 3-month prevalence rate of migraine in a health maintenance organization (HMO) population, using a 2-stage screening process and neurologist exam, and to examine the burden of illness associated with both previously diagnosed and previously undiagnosed migraine in this population. METHODS: A migraine assessment was sent to a random sample of 1,000 HMO patients between April 1999 and January 2000. Those screening positive and a random sample of those screening negative for migraine were evaluated by neurologists using a structured diagnostic assessment. Then, those diagnosed to have migraines by the study's neurologists completed a battery of 3 questionnaires, evaluating severity, distress, and impairment. RESULTS: Of 1,000 questionnaires sent, 753 (75.3%) were returned. The estimate of prevalence of migraine in this population ranged from 21.4% (adjusted for response bias) to 27.8% (unadjusted for selection bias). Only 48% of respondents had been previously diagnosed with migraine. The typical migraine caused moderate-to-severe distress in 69%, and 66% had definite or extreme interference in their social or occupational functioning. The average migraineur missed 7.6 hours of work due to migraine in the past 3 months. Previously undiagnosed migraine was associated with substantial impairment, with 58% of responders reporting interference with daily activities and 54% reporting moderate or greater distress. There was no significant difference between previously diagnosed and undiagnosed migraineurs on 3 outcome measures: pain, interference, or days of missed work. A higher proportion of previously diagnosed migraineurs (84%) reported moderate or greater distress compared with undiagnosed migraineurs (54%, P=0.002). CONCLUSIONS: Using a neurologist exam, the researchers found that the prevalence of migraine headaches was higher than previously reported. About one half of migraineurs had been previously undiagnosed. Undiagnosed migraine is associated with significant pain, distress, and dysfunction and is similar in these respects to diagnosed migraine. Increased public education and physician education on migraine are warranted.

M igraine is a common and intermittently disabling condition, causing significant burden for both the individual and society, including loss of productivity, limitations in activity, and decreased quality of life. [1][2][3][4][5] Migraine pain tends to be severe, resulting in associated symptoms and functional impairment.
In a survey of 500 self-reported migraineurs, 97% reported their headache pain to be of moderate-to-severe intensity. 6 Migraine attacks can severely impair the ability to work and require bed rest in many of the approximately 28 million affected American sufferers. 2,5,7 Migraine sufferers have more difficulty functioning at home and at work than nonmigraineurs. 3,8 A recent economic model estimated that losses due to decreased productivity are roughly $1.9 million for a company with 10,000 employees and $23.8 million for a company with 88,000 employees. 9 Epidemiologic studies have found lifetime prevalence rates of about 18% in women, 6% in men, and 4% in children in the United States, 7 with similar rates recently found in England. 10 Most studies, however, have used indirect means to determine the diagnosis of migraine, such as interviews performed by lay clinicians or self-administered questionnaires. 1 In addition, the use of different diagnostic criteria by different researchers, as well as samples confounded by age and gender differences, make comparability of results from different studies difficult to interpret.
The purpose of the current study was to examine the 3-month prevalence and disability associated with migraine in a health maintenance organization (HMO) population using a neurologic evaluation and examination by a neurologist as the gold standard to diagnose migraine. This means of diagnosis ensured the validity of the data obtained, and thus gave a more accurate estimate of the true prevalence of migraine in this population. In addition, the use of International Headache Society criteria 11 helped standardize case definition and is consistent with the more recent population-based studies. 1 Finally, the current study examined the disability associated with both diagnosed and undiagnosed migraine, which has not been well studied in an HMO population.
ss Methods Subjects Subjects were enrollees in one of the 13 separate clinics of the Dean Health Plan, a 175,000-member organization based in Madison, Wisconsin. The population of the chosen clinic (Middleton Clinic, a sample of convenience) was approximately 4,164. Subjects were considered eligible if they met the following criteria: 1. they were between 18 and 63 years old; 2. they did not have a diagnosis of a life-threatening illness or neurological condition (e.g., Huntington' s, Parkinson' s, or multiple sclerosis) that would exclude them from participation; 3. they did not have point-of-service coverage; and 4. they had been continuously enrolled in the HMO for at least 1 year.

Study Procedures
A total of 3,286 patients from the participating study clinic were identified as meeting the study eligibility requirements from April 1999 to January 2000 by examining the Dean Health Plan claims database from the previous 12 months. Of these patients, a random sample of 1,000 patients was selected. These 1,000 patients were then sent a health assessment questionnaire and a letter from the principal investigator inviting them to participate in a study on the effect of illness on quality of life. Subjects were informed that they may be invited to participate in the second step of the study based on their answers to the assessment packet and were asked to indicate if they were willing to be contacted for this study. A $5 bill was enclosed with the letter as an incentive and a goodwill gesture for their time. Subjects who did not return the assessment packet within 2 weeks were mailed a second letter and assessment packet. The health assessment questionnaire consisted of 14 yes or no questions of which 9 screened for migraine ( Table 1). The questionnaire was developed specifically for this study since no validated public domain migraine screener was available at the time of the study. A positive screen for migraine was defined as affirmation of at least 2 of the 8 migraine symptoms mentioned in the questionnaire, whereas a negative screen was defined as no symptoms or 1 symptom. Individuals who screened positive for migraine were contacted and invited to participate in the next step of the study, as was a random sample of the respondents with negative screens. Because we took only a random sample of those screens consenting to be contacted, all data were weighted to reflect this sampling design ( Figure 1). The next step in the study consisted of an in-person neurological examination by board-certified neurologists (4 independent physicians not affiliated with the study) with expertise in the diagnosis and treatment of migraine. The neurologist examination served as the standard for the diagnosis of migraine and ruled out other diagnoses that could have accounted for patient symptoms. The examination was conducted with the use of a semistructured interview guide to ensure reliability among the 4 neurologists who conducted the examinations. In addition, study neurologists attended interrater reliability training on the administration of the semistructured interview, which included viewing a video and practice administration of the interview. Examination results were reviewed by an expert consultant (author M. Dominski) and any questions were discussed and clarified.
All subjects who were diagnosed with migraine by the neurologist also completed a battery of 3 questionnaires evaluating migraine severity, distress, and impairment. All subjects signed informed-consent documents, reviewed and approved by the Dean Foundation Institutional Review Board.

Outcomes Measures
The following 3 instruments were administered (each was developed specifically for use in this study since no similar instruments were available at the time of the study): The weighted number of subjects completing the neurological exam was 336, of which 94 were migraine-positive. Of the 94 migraine-positive subjects, 79% were female and 21% were male. The mean age was 42.03 years (SD = ± 8.84; range: 19-59).

Disease Prevalence
The prevalence of migraine in this population (unadjusted for selection bias, i.e., only a random sample of negative screens was contacted) was greater than 20% (mean: 27.8%; 95% confidence interval, .26-.28, with a prevalence of 19% in males and 34% in females. Only 48% of subjects with a diagnosis of migraine on the neurological exam reported having been previously diagnosed with migraine by a health care professional. Because those with migraine may be more likely to return the mailed assessment packet, this prevalence may be inflated, with the low estimate of 21% being based on the assumption that all those who did not return the assessment packet were nonmigraineurs. An analysis of the HMO claims database found no significant difference between those who returned and those who did not return the assessment packet in the percentage of subjects with a claims diagnosis of migraine (4.7% versus 4.2%, P = 0.755) or in the percentage of subjects using triptans (3.1% versus 2.5%, P=0.657), but there was a significant difference in mean age (38.8 versus 35.6 years, P=0.001) and percent female (58.8% versus 50.0%, P = 0.016).
We also compared those consenting to be contacted with those who did not consent to be contacted in order to determine if those consenting to be contacted were more likely to have migraine and thus artificially inflate the prevalence estimates. An examination of the HMO claims database found that those who consented to be contacted had a significantly higher rate of migraine in the HMO claims database (5.8% versus 1.2%, P=0.019). We recalculated the prevalence using the most  conservative approach (i.e., we assumed that all those who did not consent to be contacted were migraine-negative). Using this approach to adjust for apparent response bias, the prevalence of migraine in this population was 21.4%. Finally, among those consenting to be contacted, there was no significant difference between those completing and those not completing the neurological examination in terms of prevalence of migraine or percentage using triptans in the HMO database. However, a small but significant difference was found in the percentage of females (67.9% versus 57.7% respectively, P = 0.036).

Pain, Distress, and Dysfunction
The average pain severity of the typical migraine rated by neurologists on the 0 to 10 HSDPI Likert scale was 7.21 (SD = 2.12; median: 8.0). When collapsed into 3 categories, 5% could be categorized as mild (0-3 on the HSDPI), 42% as moderate (4-7), and 53% as severe (8)(9)(10). On the self-report MSS, the typical migraine was rated as causing moderate distress by 43% of migraineurs, severe distress by 19%, and extreme distress by 7% (Table 2). Sixty-six percent said their migraines caused definite-to-extreme interference in their social or occupational functioning (Table 3). Only 46% reported they were "always" or "usually" successful in stopping their migraines once they felt one coming on ( Table 4). The average migraineurs missed 7.6 hours of work due to migraine in the past 3 months (SD = ±13.4), and migraine patients were limited in their activities on an average of 2.4 days in the past 3 months (SD = ±3.3). Sixty-three percent reported having at least 3 migraines over the last 3 months, and 21% reported 7 or more. Eighty-nine percent reported having migraines for longer than 2 years (median: 14 years), and 66% had migraines for 10 years or longer. Seventy-two percent had a positive family history of migraine.

Diagnosed Versus Undiagnosed Migraine
Previously diagnosed migraineurs were 89% female, compared with 71% female in the previously undiagnosed migraine group; χ 2 (1) = 4.629, P = 0.031. Mean age was 42.20 years (SD = 8.96; range: 20-56) for those previously diagnosed compared with 41.88 years (SD = ± 8.83; range: 19-59) for those previously undiagnosed, t(92) = 0.173, P = 0.863. Undiagnosed migraine was associated with substantial distress and impairment and was similar in migraine intensity and impairment as reported by patients in whom migraine had been previously diagnosed. A comparison between migraineurs who reported having been previously diagnosed with migraine by a health care professional and those who had not been previously diagnosed is presented in Table 5 and     cant difference was found between diagnosed and undiagnosed migraineurs in the percentage of headaches with head pain categorized as mild (0-3), moderate (4-7), and severe (8-10), χ 2 (2) = 4.70, P = 0.095.
No significant difference was found between diagnosed and undiagnosed migraineurs in the amount of interference the typical migraine caused with daily activities, χ 2 (4) = 5.09, P = 0.278 ( Figure 2). Fifty-nine percent of undiagnosed subjects reported definite, substantial, or extreme interference with daily activities compared with 75% for those previously diagnosed, There was a significant difference between diagnosed and undiagnosed migraineurs in the amount of distress reported, χ 2 (4) = 13.72, P = 0.008: 53.6% of undiagnosed subjects reported moderate or greater distress associated with their migraines compared with 83.9% of those previously diagnosed, χ 2 (1) = 9.34, P = 0.002 ( Figure 3).
No significant difference was found between diagnosed and undiagnosed migraineurs in hours of missed work due to migraine ( Figure 4). Subjects with undiagnosed migraine missed an average of 8 hours of work in the past 3 months due to migraine compared with 7.2 hours for patients who had been previously diagnosed, t(87) = 0.3, P = 0.76).

ss Discussion
The prevalence of migraine based on International Headache Society criteria, as confirmed by structured neurological evaluation and examination in this managed care population (21.4% adjusted for selection bias, 27.8% unadjusted), is at least as high as, if not higher than, previous epidemiologic studies of community samples. 7,14,15 Higher prevalence could be explained by several differences in methodology between the current study and previous studies.
First, this study excluded members younger than 18 and older than 65 years. Individuals in these age categories are less likely to be actively having migraine headaches, 1 but they may have been included in other study populations. Second, follow-up exams by neurologists resulted in a migraine diagnosis for some individuals who initially screened negative on the mailed assessment packet. Failing to identify this group would result in lower estimates of prevalence. Conversely, the inclusion of a structured headache interview administered by neurologists eliminated a diagnosis for participants who appeared to have migraine headaches but actually had other types of headaches.
Third, the higher rates of return of the mailed assessment packet by female members may have inflated the migraine prevalence. Finally, since this study was conducted in a single, fairly homogeneous clinic of a managed care organization, a replication study with a larger sample size and a more heterogeneous population is warranted to determine the generalizability of the results.

Prevalence and Burden of Illness of Migraine in Managed Care Patients
Comparison Between Subjects Previously Diagnosed (n = 43) and Subjects Not Previously Diagnosed (n = 51) on Interference With Daily Activities   More than half of these individuals had never been told they had migraine headaches by a health care professional despite the fact that most reported having had migraine headaches for many years, having experienced real impairment, and having had health insurance coverage. This is cause for concern, and although this study was performed in 1999, under-recognition and underdiagnosis of migraine continue to be problems today. 15 Increased public education and physician education about the symptoms and accurate diagnosis of migraine headache are urgently needed, as are simple and effective screening methods to identify patients with migraine in the family practice setting. Application of International Headache Society diagnostic criteria for migraine would be complex in this setting. However, diagnosis could be facilitated by simpler and more easily administered screening tools, such as the ones utilized in the current study. Other screens have also been reported to have good sensitivity and specificity. [16][17][18][19][20][21][22][23] Limitations of this study include the fact that these data are now 5 years old, although it seems unlikely that the prevalence or burden of migraine in managed care members is less today than it was when these data were collected. We also did not measure costs and did not calculate the financial burden of migraine. We found that previously undiagnosed migraine patients reported pain, interference with activities of daily living, and hours of missed work in similar proportion to previously diagnosed migraine patients. This suggests a potential opportunity for diagnosis and treatment of undiagnosed patients; we did not, however, assess if this potential opportunity could be fulfilled in undiagnosed migraine patients. Use of a structured screening interview such as the one used in this study may increase the identification and treatment of previously undiagnosed patients. A study identifying and treating previously undiagnosed migraine and examining the impact of treatment on patient distress, disability, and financial burden would be instructive.
In this study, previously diagnosed migraineurs did not differ from previously undiagnosed migraineurs on 3 of 4 outcome measures but did have a higher proportion of patients reporting moderate or greater levels of distress. This finding may suggest that distress more than impairment drives migraineurs to seek help from the health care system. However, undiagnosed and diagnosed migraineurs had similar, elevated levels of severity, impairment, and missed work time. Therefore, the reasons for not seeking diagnosis or treatment must be more complex than milder symptoms or less impairment (though this similarity could be the result of previously diagnosed migraineurs' having already received treatment).
The high levels of impairment and disease severity in diagnosed migraineurs also highlights undertreatment of migraine, which is still a relevant issue today. Evidence-based guidelines for the prevention and management of migraine have been published by the American Academy of Neurology (AAN) and others to assist family practitioners in generating algorithms that are appropriate for their practices. 24,25 Current treatment algorithms recommend triptans for those with moderate-tosevere migraines or poor responses to nonsteroidal antiinflammatory drugs, 6,24-26 and triptan use reduces functional disability [27][28][29][30][31][32] and is cost effective. 33,34 Preventative therapies identified by AAN as having the highest level of evidence-based efficacy and safety include antiepileptics (divalproex sodium/sodium valporate), antidepressants (amitriptyline), and beta-blockers (propranolol or timolol). Cognitive and behavioral treatments such as relaxation training, biofeedback, and cognitive behavior therapy are also recommended by AAN as possible preventative strategies.

ss Conclusions
The prevalence of migraine was high in this managed care population (34% of women and 19% of men, when unadjusted for selection bias, and 30% of women and 12% for men, when adjusted for probable response bias) compared with published population studies (18% of women and 6% of men 7,26 ). These values are very relevant to the family practice setting, perhaps even more relevant than those of general population studies since our study population comprised individuals who use the health care system. Second, disability was as high in migraineurs who had not been previously diagnosed as it was in previously diagnosed patients. This suggests that reasons for not seeking a diagnosis are more complex than the possibility that those who do not seek treatment have milder pain or disability than those who do seek treatment. Distress may be one factor that influences the decision to seek treatment since distress level was higher among previously diagnosed migrainuers. Finally, improved means for identifying and treating migraine are available and should be used in the managed care setting to the benefit of patients. Increased public and physician education about the symptoms and accurate diagnosis and treatment of migraine headache are needed.

SECTION ONE: Mild Headaches
Migraine headache attacks are often associated with certain symptoms in addition to head pain. These include nausea and/or vomiting, increased sensitivity to light and/or sound. The first section deals with migraine headache attacks where the headache PAIN is of MILD severity. Please refer to only those migraine headache attacks where the headache pain is of MILD severity when answering these questions. If none of your headache pains are MILD, that is, if the head pain was moderate or severe in all of them, skip this section and go on to Section Two (page 2).

SECTION THREE: Work and/or Home Impairment
The next three questions are about the past 3 months, not including today. 10. During the past three months, how many hours did you miss from work because of your migraine headache attacks? Include hours you missed on sick days, times you went in late, left early, etc.

INSTRUCTIONS: Please think of the PAST 3 MONTHS when answering these questions.
(Continued on next page)

Prevalence and Burden of Illness of Migraine in Managed Care Patients
Sands-Taylor Migraine Questionnaire (continued)

APPENDIX A
11. During the past three months, how much did migraine headache attacks affect your productivity while you were working? Think about days you were limited in the amount or kind of work you could do, days you accomplished less than you would like, or days you could not do your work as carefully as usual. 12. Now think about your regular daily activities (other than your job). This means the usual activities that you do every day, such as work around the house, shopping, child care, exercising, etc.
During the past three months, how much did migraine headache attacks affect your ability to do your daily regular activities? Think about days you were limited in the amount or kind of activities you could do, days you accomplished less than you would like, or days you could not do your regular activities as carefully as usual. If migraine headache attacks affected your daily regular activities only a little, choose a low number. Choose a high number if migraine headache attacks affected your daily regular activities a great deal. (Circle a number.)

SECTION FOUR: Family History of Migraine Headache Attacks
13. Does any relative related to you by blood get similar headaches?

SECTION FIVE: Medications
Please indicate whether or not you have taken any of the medications below in the PAST 3 MONTHS for migraine headache attacks and how much relief you obtained from each one.

OVER-THE-COUNTER MEDICATIONS
If taken, indicate here (by checking the box) how much RELIEF obtained.

Medication
Have you taken this medication? None Some A lot Complete 19. Ibuprofen (200 mg tablets) Which ones? (list) b.
Migraines had no effect on my daily regular activities

Prevalence and Burden of Illness of Migraine in Managed Care Patients
Sands-Taylor Migraine Questionnaire (continued)

DRUGS PRESCRIBED BY A DOCTOR
If taken, indicate here (by checking the box) how much RELIEF obtained.

Medication
Have you taken this medication? None Some A Lot Complete

Tylenol with codeine
Which ones? (list) b.___________________

APPENDIX B
We want to learn about the severity of your migraine headaches during the last three months.
When answering these questions, please refer only to your migraine headaches. Migraine headaches meet the following definition: migraine headaches last at least four hours and are associated with at least two of the following symptoms: 1) pain starting on one side of your head; 2) a throbbing or pulsating feeling in the head; 3) nausea or vomiting; 4) light or sound being more bothersome; 5) changes in vision or seeing sparkling lights; 6) numbness or tingling of your hand, arm, or face; or 7) headaches that are made worse by routine physical activity, such as walking up stairs.
Please rate only those migraine headaches that you have had in the past three months.
1. In the past three months, have you had any migraine headaches, that is, headaches that had at least two symptoms that we just described? ❑ 0 No interference ❑ 1 Slight interference with social or occupational activities, but overall performance not impaired (e.g., may skip a social activity or put off some work activity but perform most work activities) ❑ 2 Definite interference with social or occupational performance, but still manageable (e.g., attends social activities but participates less than usual; definite decrease in work performance) ❑ 3 Causes substantial impairment in social or occupational performance (e.g., does not attend important social activities; leaves work or stays home from work) ❑ 4 Extreme, incapacitating (requires bed rest) 27b) Pulsating quality 27c) Yes ❑ 1 No ❑ 0 27c) Moderate or severe intensity (inhibits or prohibits daily activities) 27d) Yes ❑ 1 No ❑ 0 27d) Aggravation by walking up stairs or a similar routine physical activity 28) During headache at least one of the following: 28a) Yes ❑ 1 No ❑ 0 28a) Nausea and/or vomiting 28b) Yes ❑ 1 No ❑ 0 28b) Photophobia and phonophobia 29) At least one of the following: 29a) Yes ❑ 1 No ❑ 0 29a) History and/or physical and/or neurological examinations do not suggest one of the following: headache associated with head trauma, vascular disorders, nonvascular intracranial disorders, substances or their withdrawal, noncephalic infection, metabolic disorder, or disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structures. 29b) Yes ❑ 1 No ❑ 0 29b) History and/or physical examinations and/or neurological examinations do suggest such disorder, but it is ruled out by appropriate investigations. 29c) Yes ❑ 1 No ❑ 0 29c) Such disorder is present, but migraine attacks do not occur for the first time in close temporal relation to the disorder.
2.1 Migraine with aura (Aura as herein used does not necessarily imply that it precedes the headache, nor does it imply any relationship with epilepsy.) Diagnostic Criteria

31)
Yes ❑ 1 No ❑ 0 31) At least 2 attacks fulfilling 32a-32d 32) Yes ❑ 1 No ❑ 0 32) At least 3 of the following 4 characteristics: 32a) Yes ❑ 1 No ❑ 0 32a) 1 or more fully reversible aura symptoms indicating focal cerebral cortical and/or brain stem dysfunction 32b) Yes ❑ 1 No ❑ 0 32b) At least 1 aura symptom develops gradually over more than 4 minutes, or 2 or more symptoms occur in succession. 32c) Yes ❑ 1 No ❑ 0 32c) No aura symptom lasts more than 60 minutes. If more than 1 aura symptom is present, accepted duration is proportionally increased. 32d) Yes ❑ 1 No ❑ 0 32d) Headache follows aura with a free interval of less than 60 minutes. (It may also begin before or simultaneously with the aura.) 33) At least 1 of the following: 33a) Yes ❑ 1 No ❑ 0 33a) History and/or physical examinations and/or neurological examinations do not suggest one of the following: headache associated with head trauma, vascular disorders, nonvascular intracranial disorders, substances or their withdrawal, noncephalic infection, metabolic disorder, or disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structures. 33b) Yes ❑ 1 No ❑ 0 33b) History and/or physical examinations and/or neurological examinations do suggest such disorder, but it is ruled out by appropriate investigations. 33c) Yes ❑ 1 No ❑ 0 33c) Such disorder is present, but migraine attacks do not occur for the first time in close temporal relation to the disorder.

35)
Migraine with aura ❑ 1 35) If patient meets criteria for both migraine with and without aura, which occurs most frequently? Migraine w/o aura ❑ 2